Mammalian cytokines; receptors; related reagents and methods

Abstract

Nucleic acids encoding mammalian cytokine receptor, e.g., for cytokine IL-B50, purified proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

What is claimed is: 
     
         1 . A method of producing a ligand:receptor complex, comprising contacting:
 a) a substantially pure or recombinant mammalian IL-B50 with a receptor comprising the IL-7Rα or the Rδ2 subunit;   b) a mammalian IL-B50 with a receptor comprising a substantially pure or recombinant IL-7Rα subunit; or   c) a mammalian IL-B50 with a receptor comprising a substantially pure or recombinant Rδ2 subunit;   
       thereby allowing said complex to form. 
     
     
         2 . The method of  claim 1 , wherein:
 a) said mammalian IL-B50 is primate IL-B50;   b) said complex formation results in signal transduction, STAT activation, or TARC, PARC or MDC expression;   c) said receptor is on a cell;   d) said receptor comprises both IL-7Rα and Rδ2 subunit;   e) said complex formation results in a physiological change in the cell expressing said receptor;   f) said contacting is in combination with a proliferative agent, cytokine, or chemokine; or   g) said contacting allows quantitative detection of said ligand.   
     
     
         3 . The method of  claim 2 , wherein said receptor is on a hematopoietic cell, including a lymphoid lineage cell, myeloid, or dendritic cell. 
     
     
         4 . A method of modulating physiology or development of an IL-7Rα or Rδ2 expressing cell comprising contacting said cell to an exogenous agonist or antagonist of a mammalian IL-B50. 
     
     
         5 . The method of  claim 4 , wherein:
 A) said antagonist is:
 1) an antibody which neutralizes said mammalian IL-B50; 
 2) a mutein of said IL-B50; or 
 3) an antibody which binds to IL-7Rα or Rδ2 or a complex comprising both; 
   B) said physiology is selected from:
 1) proliferation; 
 2) lymphoid or dendritic lineage cell development; 
 3) antigen presentation; or 
 4) production of inflammatory mediators, including cytokines, chemokines, or adhesion molecules; or 
   C) said cell is a hematopoietic cell.   
     
     
         6 . The method of  claim 4 , wherein:
 a) said antagonist is an antibody and said physiology is hematopoietic cell proliferation;   b) said agonist is IL-B50 and said physiology is hematopoietic cell differentiation; or   c) said physiology is antigen presentation.   
     
     
         7 . The method of  claim 4 , wherein said modulating is blocking, and said physiology is lymphoid lineage cell proliferation. 
     
     
         8 . A method of modulating a signal to a cell mediated by IL-B50 comprising contacting said cell to an administered agonist or antagonist of IL-B50. 
     
     
         9 . The method of  claim 8 , wherein said modulating is inhibiting, and said signal is a proliferation signal. 
     
     
         10 . The method of  claim 9 , wherein:
 a) said antagonist is a neutralizing antibody to IL-7Rα or the Rδ2 subunit or a complex comprising said subunits;   b) said agonist or antagonist is administered in combination with another antagonist or agonist of IL-B50; or   c) said agonist or antagonist is administered in combination with a growth factor, cytokine, chemokine, or immune adjuvant.   
     
     
         11 . The method of  claim 9 , wherein said contacting is with another anti-proliferative agent or treatment. 
     
     
         12 . A method of selectively labeling a population of cells, said method comprising contacting said cells with an antibody which binds:
 a) IL-7Rα;   b) Rδ2; or   c) a complex comprising one of said subunits;   
       thereby resulting in the identification of cells expressing said subunit or complex. 
     
     
         13 . The method of  claim 12 , wherein:
 a) said contacting results in modulation of STAT activation;   b) said labeling allows purification of IL-7Rα or Rδ2 subunit expressing cells; or   c) said labeling allows depletion of IL-7Rα or Rδ2 subunit expressing cells.   
     
     
         14 . A population of cells made by the method of  claim 13 . 
     
     
         15 . The population of  claim 14 , which are prepared by Fluorescent Activated Cell Sorting. 
     
     
         16 . A method of testing a compound for ability to affect receptor-ligand interaction, said method comprising comparing the interaction of a receptor complex comprising IL-7Rα and/or Rδ2 subunit with IL-B50 in the presence and absence of said compound. 
     
     
         17 . The method of  claim 16 , wherein said compound is an antibody which binds one of:
 a) IL-7Rα;   b) Rδ2 subunit;   c) a receptor comprising IL-7R and/or Rδ2; or   d) IL-B50.   
     
     
         18 . An isolated or recombinant protein complex comprising:
 a) at least 15 contiguous amino acid residues of SEQ ID NO: 2 and at least 15 contiguous amino acid residues of SEQ ID NO: 4;   b) at least two distinct segments of at least 8 contiguous amino acid residues of SEQ ID NO: 2 and at least two distinct segments of at least 8 contiguous amino acid residues of SEQ ID NO: 4; or   c) at least one segment at least 21 contiguous nucleotides of SEQ ID NO: 1 and at least one segment at least 21 contiguous nucleotides of SEQ ID NO: 3.   
     
     
         19 . The complex of  claim 18 , wherein:
 a) one of said segments of SEQ ID NO: 2 is from the extracellular portion of said sequence;   b) one of said segments of SEQ ID NO: 4 is from the extracellular portion of said sequence; or   c) said polypeptide comprises the mature SEQ ID NO: 2 and the mature SEQ ID NO: 4 sequences.   
     
     
         20 . An isolated or recombinant polynucleotide encoding said complex of  claim 19 , wherein:
 a) said polynucleotide comprises a deoxyribonucleotide;   b) said polynucleotide comprises a ribonucleotide; or   c) at least one of said segments is operably linked to a promoter.   
     
     
         21 . A binding compound comprising an antigen binding portion from an antibody which binds with selectivity to a polypeptide comprising at least 12 contiguous amino acid residues of SEQ ID NO: 2 and at least 12 contiguous amino acid residues of SEQ ID NO: 4; said polypeptide encoded by a nucleotide of  claim 20 .